For EuroPDX CRC liver metastasis data, raw copy number profiles for each sample were estimated using the QDNAseq75 R package (version 1.20) by dividing the human reference genome into non-overlapping 50-kb windows and counting the number of reads (see Supplementary Methods) in each bin. Bins in problematic regions were removed76. Read counts were corrected for GC content and mappability using a LOESS regression, median normalized and log2 transformed. Values below –1,000 in each chromosome were floored to the first value greater than –1,000 in the same chromosome. Raw log2[ratio] values were then segmented using the ASCAT33 algorithm implemented in the ASCAT R package (version 2.0.7). For EuroPDX BRCA tumors, raw copy number profiles were estimated for each sample by dividing the human reference genome into non-overlapping 20-kb windows and counting the number of reads (see Supplementary Methods) in each bin. Only reads with a mapping quality of at least 37 were considered. Bins within problematic regions (that is, multimapper regions) were excluded. Downstream analysis to estimate copy number was conducted as described above.

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